Primary and acquired EGFR T790M-mutant NSCLC patients identified by routine mutation testing show different characteristics but may both respond to osimertinib treatment

• Published in: Cancer letters 2018-06, Vol.423, p.9-15
• Main Authors: Li, Weihua, Qiu, Tian, Guo, Lei, Ling, Yun, Gao, Yibo, Ying, Jianming, He, Jie
• Format: Article
• Language: English
• Subjects: Acquired EGFR T790M mutation; Acrylamides; Adult; Age; Aged; Aged, 80 and over; Aniline Compounds; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Deoxyribonucleic acid; Diagnostic Tests, Routine; DNA; Drug Resistance, Neoplasm; Drug therapy; Enzyme inhibitors; Epidermal growth factor receptors; ErbB Receptors - genetics; FDA approval; Female; Females; Gender; Gene frequency; Humans; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Male; Middle Aged; Multivariate analysis; Mutant allele frequency; Mutation; Non-small cell lung cancer; Non-small cell lung carcinoma; Patients; Piperazines - administration & dosage; Piperazines - therapeutic use; Population genetics; Primary EGFR T790M mutation; Progression-Free Survival; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - therapeutic use; Protein-tyrosine kinase; Retrospective Studies; Sensitizing EGFR mutation; Sequence Analysis, DNA; Targeted cancer therapy; Treatment Outcome; Tumors; Young Adult
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2018.03.005

Primary EGFR T790M mutation is occasionally identified by routine mutation testing in tyrosine kinase inhibitor (TKI)-naive patients with non-small cell lung cancer (NSCLC). We herein aimed to compare the characteristics of primary and acquired T790M mutations in NSCLC patients, and their response to osimertinib. Using amplification refractory mutation system (ARMS) detection, primary T790M was identified in 0.5% (46/8723) of TKI-naive patients, whereas acquired T790M was detected in 49.7% (71/143) of TKI-relapsed patients. T790M always coexisted with a sensitizing EGFR mutation. Primary T790M more commonly coexisted with L858R, whereas acquired T790M was more likely to coexist with exon 19 deletions. Moreover, next-generation sequencing (NGS) showed that concomitant sensitizing EGFR and primary T790M mutant allele frequencies (MAFs) were highly concordant, but acquired T790M MAFs were significantly lower than the sensitizing EGFR MAFs. Sixteen acquired T790M-mutant patients received osimertinib. The median progression-free survival (PFS) was 8.1 months. Four primary T790M-mutant patients received osimertinib and the median PFS was 8.0 months. Together, our study demonstrates that primary and acquired T790M-mutant patients show distinct differences in some clinical and molecular characteristics, but may both respond to osimertinib treatment. •Primary EGFR T790M was identified in 0.5% (46/8723) of TKI-naive patients by ARMS.•Primary EGFR T790M was more likely to coexist with L858R, but acquired T790M was more likely to coexist with exon 19 del.•Concomitant sensitizing EGFR and primary T790M MAFs were highly concordant.•Acquired T790M MAFs were significantly lower than the sensitizing EGFR MAFs.•NSCLC patients with primary or acquired EGFR T790M may benefit from osimertinib.